Resveratrol and Small Artery Compliance and Remodeling in the Spontaneously Hypertensive Rat

Behbahani, John; Thandapilly, Sijo Joseph; Louis, Xavier Lieben; Huang, Yingsu; Shao, Zongjun; Kopilas, Melanie A.; Wojciechowski, Peter; Netticadan, Thomas; Anderson, Hope D.

doi:10.1038/ajh.2010.161

Cited by 50 publications

(44 citation statements)

References 37 publications

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“…Although a low dose of resveratrol (2.5 mg/kg/day) alone did not affect the systolic or the diastolic pressure in the SHR [31,39], the combination of hydralazine and resveratrol treatment was significantly more effective than hydralazine alone in reducing both systolic and diastolic BP [31]. Although these findings are important, hydralazine is rarely used in the clinic to treat hypertension.…”

Section: Preclinical Studiesmentioning

confidence: 63%

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Zordoky

Robertson

Dyck

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

271

217

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Cardiovascular disease is the leading cause of death worldwide. Despite advancements in diagnosis and treatment of cardiovascular disease, the incidence of cardiovascular disease is still rising. Therefore, new lines of medications are needed to treat the growing population of patients with cardiovascular disease. Although the majority of the existing pharmacotherapies for cardiovascular disease are synthesized molecules, natural compounds, such as resveratrol, are also being tested. Resveratrol is a non-flavonoid polyphenolic compound, which has several biological effects. Preclinical studies have provided convincing evidence that resveratrol has beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. Although not fully delineated, some of the beneficial cardiovascular effects of resveratrol are mediated through activation of silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and endogenous anti-oxidant enzymes. In addition to these pathways, the anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties of resveratrol contribute to its beneficial cardiovascular effects. Despite the promise of resveratrol as a treatment for numerous cardiovascular diseases, the clinical studies for resveratrol are still limited. In addition, several conflicting results from trials have been reported, which demonstrates the challenges that face the translation of the exciting preclinical findings to humans. Herein, we will review much of the preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular disease and provide information about the physiological and molecular signaling mechanisms involved. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

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Section: Preclinical Studiesmentioning

confidence: 63%

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Zordoky

Robertson

Dyck

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

271

217

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“…Improved NO bioavailability in the vasculature has been proposed to be an important mechanism by which continued Resv supplementation improves cardiovascular function 9,10,18 and prevents pathological vascular remodeling. 19 The finding that l-NAME caused a greater rise in BP, effectively normalizing BPs between SHR and SHR+Resv, suggests that a key mechanism by which Resv causes long-term BP normalization is restoration of NO-mediated signaling. To gain insights into the effects of maternal Resv treatment on adult offspring vascular function, we assessed hemodynamic responses to the endothelial-dependent vasodilator MCh in the presence and absence of l-NAME.…”

Section: Discussionmentioning

confidence: 99%

Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring

et al. 2016

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ypertension is an important and modifiable risk factor for cardiovascular disease, affecting ≈1 in 4 adults worldwide. 1 In the United States, hypertension is estimated to account for >$46 billion annually in healthcare services, medication, and lost productivity, 2 and these costs are expected to increase substantially over the coming decades. A universal consensus is that prevention, rather than treatment, is a more strategic and cost-effective approach to reducing the burden of cardiovascular disease in coming decades.Essential hypertension, in which known primary causes (eg, renovascular disease, pheochromocytoma, monogenic causes, etc) are not present, makes up 95% of hypertension worldwide.3 Although the pathogenesis of essential hypertension is multifactorial and complex, subclinical changes in vascular function often precede the development of hypertension and circulatory decline. 4 The spontaneously hypertensive rat (SHR) is a model of essential hypertension in which blood pressure (BP) begins to rise after 6 weeks of age, ultimately reaching stable pressures of ≈180 to 200 mm Hg. Recently, Komolova et al reported evidence of altered vascular resistance profiles and renal hemodynamics as early as 3 weeks of age in the SHR, 5 implicating these early functional changes as a cause, rather than a consequence, of hypertension in this model. As such, the developmental period before weaning (ie, See Editorial Commentary, pp 829-830Abstract-This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (−18 mm Hg; P=0.007), and nitric oxide synthase inhibition (with l-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment with l-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric art...

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“…To cardiac hypertrophy Resveratrol did not lower high blood pressure directly in the spontaneously hypertensive rat, but it attenuated compliance and remodeling of small artery [106,107]. Regression of pressure overload-induced cardiac hypertrophy and dysfunction has been reported in resveratroltreated abdominal aortic-banded rats [108].…”

Section: Resveratrol In Cardiovascular Remodeling and Heart Failurementioning

confidence: 96%

Resveratrol in cardiovascular disease: what is known from current research?

et al. 2011

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Resveratrol is a well-known antioxidant that exists in grape skin/seed, red wine, and the root of Polygonum cuspidatum, a traditional Chinese and Japanese medicinal material. Studies have found that resveratrol has many interesting properties, including anti-carcinogenic properties, anti-microbial and antiviral effects, the ability to reverse dyslipidemia and obesity, the ability to attenuate hyperglycemia and hyperinsulinemia, and the ability to protect endothelial function. Heart failure is the final consequence of the majority of cardiovascular diseases, and resveratrol has been shown to directly attenuate heart contraction. The cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. This article will mainly review recently published basic researches about the protective cardiovascular effects of resveratrol because these results may lead to the development of new clinical therapeutics in patients.

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Resveratrol and Small Artery Compliance and Remodeling in the Spontaneously Hypertensive Rat

Abstract: The ability of resveratrol to limit the increase in compliance of SHR arteries is likely related to inhibitory effects on remodeling and pro-growth ERK signaling rather than blood pressure or arterial wall component stiffness.

Cited by 50 publications

References 37 publications

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring

Resveratrol in cardiovascular disease: what is known from current research?

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